Lipoprotein analysis is useful for estimating the risk for coronary artery disease and for assessing the effectiveness of cholesterol lowering therapy. The overall objective of this project is to improve the analytical performance of current lipoprotein assays and to potentially develop new lipoprotein tests with improved diagnostic accuracy. In the past year, we have completed a study on a series of serum samples in the following 4 categories: (1) High HDL-C (>80 mg/dL) with cardiovascular disease (CHD) (N=58), (1) High HDL-C (>80 mg/dL) with no CHD (N=58), (1) Low HDL-C (< 30 mg/dL) with CHD (N=47), (1) Low HDL-C (< 30 mg/dL) with no CHD (N=58). All subjects have LDL-C< 130 mg/dL and are on no lipid lowering medications. HDL is a cardioprotective risk factor and is usually measured by its cholesterol content (HDL-C). HDL, however, is composed many other constituents and exists in at least 12 different subfractions and some forms of HDL, such as oxidized HDL are believed to be dysfunctional. The specific goal of this study is to determine whether some other parameter for measuring HDL besides HDL-C may better a predictor of cardiovascular disease. Both the protein and lipid composition of the various HDL groups were found to be similar except that there was a statistically significant increase in the content of apoE from the high HDL group with CHD. By non-denaturing gel electrophoresis, no difference was observed in HDL subfractions between the groups but patients with CHD for both the high and low HDL group had an approximate 25% increase in intermediate density lipoproteins. Tests for both remnant-cholesterol and remnant-triglyceride confirmed this finding. Future studies will be aimed at examining cholesteryl ester transfer protein polymorphisms in the 4 groups to assess its possible interaction between HDL metabolism, remnant lipoproteins, and cardiovascular risk.